The objective of the proposed research is to explore the role of collagenase in collagen breakdown and to learn how this breakdown is controlled by pharmacologic doses of steroid hormones. These studies will involve the involuting rat uterus, an organ known to show extremely rapid breakdown of collagen. Methods have been developed for assaying collagenase directly in tissue homogenates of this organ and for extracting collagenase from the tissue. It has also been shown that treating parturient rats with estradiol reduces the assayable levels of uterine collagenase with a consequent reduction of collagen breakdown. It is proposed to study two occult forms of collagenase in the uterus. One form appears to be masked by a collagenase inhibitor and the second form may represent a zymogen of collagenase. The second form appears to increase as free collagenase decreases in response to estradiol treatment. The use of direct tissue assays will permit the evaluation of hormonal effects on collagenase in the intact animal, as opposed to the current methods which are largely limited to tissue culture techniques. Testosterone and progesterone will also be tested to see if their known effects of increasing the collagen content of the involuting uterus are due to an inhibition of collagen breakdown and a depression of collagenase levels, as in the case of estradiol. The development of direct methods for collagenase assay and the possible pharmacologic control of collagenase activity by hormone treatment should be of wide interest in connection with such problems as wound healing, bone resorption, arthritis, cancer invasiveness, gingivitis and corneal burns. BIBLIOGRAPHIC REFERENCES: Woessner, J.F., Jr., Sapolsky, A.I., Morales, T. and Nagase, H. Proteinases that digest the connective tissue matrix. Absts. II International Symposium and Intracellular Protein Catabolism, Ljubljana, May 26-30, 1975. pp. 61-63. Woessner, J.F., Jr. Regulation of collagenase activity. Scand. J. Rheumatology Suppl. 8, Abst. 15-03, 1975.